Patrick Short  0:03  
Hi everyone and welcome to the genetics Podcast. I'm really excited to be here today with Baroness Blackwood who is the chair of genomics England and was the first female MP for Oxford. And she was elected by MPs of all parties to chair the common science and technology select committee. Prior to all of this, both of Nicholas parents worked in medicine or father was a medical doctor. Her mother was a nurse. And she studied actually music, not biology, or genetics or anything we're going to talk about today at St. Anne's College and Oxford. And she later studied for an MPhil degree in musicology Emmanuel College and Oxford. We're gonna talk today about Nikolas role in science and technology, in particular, the genomics and personalised medicine movement, if you'd like to call it that here in the UK over the past decades, and also what the future might look like, so Nicola, with that introduction, first of all, thank you so much, and excited to be here with you. Hi, Patrick. It's great to be here. Thank you for having me on board. So what sparked your interest initially in you studied music, and then you moved into public policy and then ultimately have played a pivotal role in public policy, the intersection between public policy and science and genomics in particular, so what sparked that interest in and got you to start on that path? Well, I never really had a chance. But to be interested, I think my earliest memory is sitting on my father's lap, maybe at about the age of three or four, and him explaining to me the principles of circulation with a pretty old book, which had Harvey's original drawings in it. And then like at the breakfast table a few years later, him explaining the immune system using my rice krispies as a kind of visual aid. So I was pretty much kind of had sort of medical and clinical principles instilled in me from a young age, I think my first job that was helping my dad in his testing clinic, cardiac testing clinic, sort of helping ferry patients around and explaining to them what the tests would be and what they would mean. So I was pretty embedded in in that world. But you know that there's other parts of me the other side of my brain loved music. So I was the black sheep of the family went into a completely different world. But I always had this side of me, that felt as though I wasn't quite living up to the vocational and helping people reputation that my parents had, had built up. My parents were extraordinary. I, when I was about seven, I saw them resuscitating a patient in an airport and that patient getting up and getting onto the plane, it was like they were gods or something. And so when I got into parliament, politics, and represented Oxford, one of the most research and science heavy constituencies in the country, Cambridge can argue with me on that, but I'm pretty sure that's true. It was very natural. But I wanted to make sure that I stood up for science, I stood up for evidence based policymaking, and I made sure that there was a voice for research and development. And one of the things that really shocked me was that many scientists didn't feel as though they have that voice. And gradually, that became more and more a part of my day to day work until I became the Chair of the Science Technology select committee. And one of the things that also struck me, I heard you speak, I think, for the first time at a genomics a rare disease conference in Cambridge. And we can, we won't have that argument about Cambridge or Oxford today. But rare disease and genomics in particular has been an important issue to you. And I did my PhD in rare childhood developmental disorders. And since I started that in the mid 2010s, to now, the UK in particular, and we can talk a little bit about where the rest of the world is out on this. But the UK in particular has come a very long way to really being on the cusp of universal whole genome sequencing for patients with rare disease. I wonder if you could talk a little bit about where we were on that particular challenge when you started your, your career and how much has changed from then to now. 

Baroness Nicola Blackwood  3:56  
So well, I don't want my experience and then I'll talk about the national picture. So I've had a lifelong challenge with my health, which I didn't understand or know had anything to do with rare diseases. It took me 30 years to get diagnosed a standard diagnostic odyssey. All patients who experienced this will recognise the bouncing around the health system. I had lots of different diagnostic tests, which have nothing to do with what is wrong with you, clinicians being very determined to diagnose you and then reaching a dead end and then saying, you know, I think perhaps this might be in your head. And then eventually I happened to meet an extraordinary neurologist with experience of the form of Ehlers Danlos, which I have, he recognised just from my medical history that this might be what was going on, referred me to the right specialist who diagnosed me within 20 minutes after 30 years. And I was really quite sick at this point. And I was already a member of parliament and then went on the process of having to find the right treatment regime because of course, like many rare diseases, there is

is no therapeutic arts what's wrong with me there's only 25% of rare diseases actually have a specific therapeutic. And we have about 7000 known rare diseases, there are probably many more, which we don't know about. And so that made me much more aware of the national situation. For patients with rare diseases, the average time to diagnosis in the UK is five to seven years. For many like me, it's much longer. And so when I started in politics, there were some activities, which were trying to address this such as the 100,000 Genome Project, which started in 2013. And which has had an extraordinary impact. And I know we're going to talk about that a bit later. But in other areas, such as wider activity in order to improve the diagnostic process to support those who are undiagnosed within the system, to coordinate care for patients who are trying to navigate their way through systems where they have multiple conditions, or multiple outcomes from their condition. So they need to have many different consultants and have to be treated at more than one hospital at a time, the the system was really broken. Now we have heredity framework, which is working very hard to try and improve it. But we still have a long way to go. And what has made me very proud is that we've gone from Rare Disease really being not just the Cinderella of the health system, but the Cinderella of the Cinderella of the health system to now being a priority. And not just within improving diagnostics, improving care pathways, but also finding a way to make therapeutics and diagnostics affordable. Because this requires new reimbursement pathways.

Patrick Short  6:40  
Yeah, I'd love to get your thoughts on the reimbursement pathways. And then maybe we can talk a little bit about genomics England 100,000 genomes, but it's a topic that I'm I'm really interested in, because I see this, on the one hand major technology shift. If we've got gene editing, we've got fundamental improvements in the understanding of biology, that mean we can cure previously incurable diseases. But then on the other side of this, we have a healthcare system that we know, is already struggling to pay for everything that it needs to pay for, without having million dollar cures for the 1000s of diseases that we actually know need them. I'm interested in your thinking on how we square that big challenge we have in front of us of the transformative medicines that are being priced as hundreds of 1000s to millions of, of dollars for what is ultimately a very transformative impact, but maybe not one we can afford if it is applied to everybody.

Baroness Nicola Blackwood  7:33  
No. And I mean, we have to be straightforward about this. No country has solved this problem yet. But there are some early models, which have been looking about value based pricing instead of volume based pricing. And I think that that should be explored. And one of the biggest challenges is looking at how you can roll out therapeutics while the data is not necessarily there. And understanding, you know, the ethical question where there is no therapeutic in the market. So we do have some existing solutions where you wouldn't get through the normal clinical pathways. So there's the early access to medicine scheme, which is basically a compassionate scheme. Now, that has allowed many patients to access therapeutics where you wouldn't ordinarily, the challenge with that is that most of the risk, if not all of the risk is usually borne by the pharmaceutical or biotech company. And in other countries, there is more of a shared risk basis. So I think we need to start looking at some of those alternative models to maybe open up that we've also the MHRA, the regulator has brought in an accelerated pathway Ilac, for innovative medicines, which has been I mean, it's only been open for about 18 months, 120 applications have gone through that the vast majority have been successful in a very short amount of time. So that's really encouraging. We're driving innovation through Pathways, and that's for diagnostic products, as well as therapeutics. And then at the other at the other end, we have to look at the IMF, the innovative medicines Fund, which I was, was sort of my baby, right in the beginning when I was in the departments, I'm pleased that it's happened, that the devil is always in the detail in the design of these things as to how many therapeutics get through it. It's it's designed off the model of the cancer drugs fund. And the whole point of that was where you have therapeutics where you need to prove prove efficacy and affordability while in the market, because until they're actually in the market, you can't demonstrate that. So you gather data while in use, but you don't want to hold it back and you won't be able to demonstrate it until it's in use. And so the point of the IMF is for those non cancer drugs, including rare disease drugs to go through to go through a route like that. It is a reasonable amount of money. It's it's 640 million but it's so far 100 million, but we have, we have to see how it works in practice, and review its efficacy to see if it meets meets the challenge which were presented with which you're talking about. But it is not it's, but it's a plaster, it's not a long term fix for the wider challenge, what we need is a way for the curative medications to get through. And so I think we need to be looking at risk sharing models, which, you know, are value based rather than the volume base models.

Patrick Short  10:28  
With your genomics England hat on maybe you can tell many people will be familiar with genomics seeing that and what it does, it'd be great to hear from you. In particular, the mission, as it started off, was really focused around the 100,000 genomes programme, and had a real focus on rare disease and cancer. And at least from my perspective, in the last couple of years, that mission has continued to broaden beyond just delivery of the 100 Genomes Project to also include that bringing genomics into the health care system in the UK. More broadly, I'd love to hear how you got involved as the as the chair, what drew you to it, and then maybe you could tell everybody a little bit about the future there. And we have heard from Chris on the podcast before so people can go back and listen to that episode with Chris and Richard Scott, if they want to hear it from from Chris's perspective as well.

Baroness Nicola Blackwood  11:14  
Well, I'm sure they will have given you know all the detail. But the mission, essentially, of genomics, England, is to ensure that genomics based healthcare is available for everyone anywhere. So this is why we have the UK are sort of ahead, because we bring an equitable access to health care throughout the NHS. And you know that the 100,000 Genome Project was a research based project, which demonstrated that whole genome sequencing could have value in the healthcare system for patients with cancer or rare diseases. And the evidence out of that prove that this was the case. And during the pandemic, extraordinarily, we rolled out the genomics medicine service, delivering whole genome testing for rare disease and cancer patients as a standard of care. And nowhere else in the country does that across and nowhere else in the world does that across an entire healthcare system. But the really exciting thing I think about genomics England, is that, you know, genomics England sits in the centre of what we call it an infinity loop. And we feed back the clinical research data into our centrally held data set. And then we allow, in a safe way, as a reading library, not a lending library, our researchers and industry partners to interrogate that data to find discoveries for new diagnostics and new therapeutics which are so desperately needed, and to drive those discoveries back into the clinical system. And it is that ever faster moving loop of discovery into clinical care back in discovery into the clinical care, which means that I always say we are providing the hope to those patients who are on that diagnostic odyssey that we will bring that Odyssey to an end and for cancer patients, of course, we can make sure that they are directed into the best and most effective care in the first place, rather than going perhaps on a journey to the wrong care and risking poor outcomes, which has so often happened within the care system. And this is a very pressurised system. So if we can do anything to improve that, that it is the right thing to be doing. I always say kind of, well, the hope within the NHS at the moment.

Patrick Short  13:26  
Yeah, it's tremendous. I had a question actually about how you all at genomics England and really in UK, Science and Technology Policy in general, where where do you look for inspiration because I know that many countries actually looked in genomics England for inspiration as they're setting up their own infinity loop programmes and their own healthcare systems because that programme is a couple of years ahead, where where most others are but interested in where what what other examples that are maybe doing it differently than the UK do you all look to and and learn from, as you're thinking about? How do we design these kinds of programmes going forward?

Baroness Nicola Blackwood  14:04  
Well, there are some amazing other other programmes around the world. But one of the things about genomics England, which we probably don't talk about enough is that we're not we're not a institution that is just based in the UK, we're actually a global community of genomics, clinicians and researchers. So we have about three and a half 1000 genomics experts who are based in what we call g snips, which are groups of experts who are grouped into areas of specialism so it might be melanoma or it might be lung cancer, it might be a specific rare disease, or it might be a cross cutting areas such as applying machine learning it so that we can get clinical insights faster out of the data. And it is by gleaning the insights of these experts from around the world that we upgraded improve the performance of a platform and the service for patients all the time. I mean, it's a, it's a continuous sense of improvement. And obviously the team go around the world all the time to try and find out how we can go to the road or we go to all different places to make sure that we can always get that it's cutting edge. We also developed a recent partnership with NC tro, to see if we can develop really targeted algorithms on the data because the larger our data gets, as we bring more and more patient datasets into the dataset, the more challenging it is to return those really insightful diagnoses to patients as quickly as possible. And that is what we're all about in the end. The other element is, of course, that we have added two more research programmes to our task, because we always want to stretch ourselves, which are really at the cutting edge of where genomics is at the moment. One is validating new forms of cancer technologies. These would be for example, on MRI technologies, like Oxford Nanopore. And we're really excited about the potential of that to have kind of different forms of technologies, finding the quickest and most sophisticated answers for patients and different kinds of patient profiles will require different kinds of responses. So you might have a bedside analysis plus a whole genome, we're looking at what will be the best, and that's our cancer 2.0 programme, you can find out about it on the website. And the other is our newborn genomes programme, where we will be doing a research programme of of sequencing 100,000 newborns to see how we can shortcut entirely the diagnostic odyssey for those for those children with rare diseases, who so often have maybe four or five years of diagnostic odyssey, and sadly, many of them may even die before they get a diagnosis. And so we believe that, you know, 1000s of patients will benefit from that. And for their families, it will be so incredibly meaningful.

Patrick Short  17:04  
Yeah, I can't agree more both. In both of those cases, I think the newborn screening, the benefit is going to be incredible for meaningful number of percentage points of people that come through the programme. But then there's also the additional benefit of starting to take a really different approach to early prediction and screening that I know opens up some enormous ethical challenges as well, the thing that's impressed me about that programme is it is probably the I know, it's not the first newborn screening programme, but it's one of the first set this scale, and comprehensiveness of testing and the thoughtfulness of the approach taken to actually really map the boundaries of what do we want to return? What shouldn't we return under what circumstances because it is a, it's there's quite a profound set of outcomes that are possible from the extremely helpful finding to the extremely devastating, untreatable finding that you really will struggle to counsel patients and participants on the range of possible outcomes as well. And so how you, I'm just I guess, I'm impressed that that project is moving at the speed it is because it's a very easy one to actually just get overwhelmed by the sheer possibilities of what could go wrong. And then and then not get started. But it seems like there's some really good leadership to actually take one step at a time because the outcome of this, I'm convinced will be very positive. But it's going to be a challenge along the way,

Baroness Nicola Blackwood  18:26  
is it's very important to understand that discussions about how a programme like this could be approached ethically, and operationally safely have been thought about and discussed for as long as since 2017, when I was at the life sciences minister in the comments. So this hasn't just come out of nowhere. It's just that this was funded for this comprehensive spending review period, which I'm really proud about. Because I think for those patients who can't get the diagnosis, and who basically live their childhood lives undiagnosed, and in hospitals, this is the most extraordinary benefit and will be hugely life changing in terms of quality of life. You are right. However, it is important to make sure that firstly, consent is approached in a sensitive way, given the context. Second, and I would say that our genomics England has an outstanding record in terms of patient consent and approach. At the moment in our genomics Medicine Service. We have a 95% Consent consent rate for research, which shows that it is approached sensitively appropriately and takes into account the context in which those questions are asked the second thing that I would say is that we are only going to return to patients results which can be clinically acted on at the time. So it this is not going to return results which would have you know, create anxiety but no one can do anything about it because that is not considered an ethical outcome.

Patrick Short  19:59  
Make sense? And but hopefully it opens up the research avenue to understand how because I'm interested in the issue, there's a whole range of actionability beneath clinical actionability, right life planning. If you know that, for example, return of a. Appleby for result is may not be clinically actionable today. But under the right circumstances, someone if they're 50 years old may want to know that because it helps them to plan their life. And I think it's the right choice to not have that be part of the newborn screening programme. But it's an interesting set of long term discussions you're going to have how do we approach some of these genetic findings that might be secondary to the newborn screening findings that could have a be either clinically useful or otherwise useful for the participants later on in life.

Baroness Nicola Blackwood  20:49  
So later discussions about other other kinds of research approaches will be discussed. But this is a clinical programme at this stage. So a research programme would be as a second discussion, this is specifically targeted programme. At this stage,

Patrick Short  21:04  
I want to pick up on the different pillar of genomics England and UK personalised medicine strategy, which is supporting startups and scaleups. I know that this is something that you personally have a have a real interest in, I'm interested to hear the thinking behind explicitly, including supporting startups and scaleups intermission because from the startup scale up perspective, it's really meaningful to have large organisations that are that are working to bring some of the new approaches or technology and I'm interested in how that embeds itself through the UK scientific technology landscape more generally, because I think the UK again, is leading in many ways on bridging that gap between new new companies with new technologies and getting them out to scale through the healthcare system, or even more broadly, in the economy.

Baroness Nicola Blackwood  21:52  
So one of the things that I think people miss a little bit is that genomics England itself is a scale up, which is how we feel the pain of so many genomics and other startups and scale ups within the UK Life Sciences ecosystem, and therefore make the case a lot for improvement of the innovation ecosystem and adoption ecosystem within the NHS, and have a very personal understanding of where a lot of the friction points are. So the first thing I would say is, we have you know, two great champions in John Simons and John Bell, who have written and the life sciences vision and genomics is a key pillar of the life sciences vision to be delivered as a way that we can not just make sure that the life sciences sector thrives, and that there are various different parts of the climate which is improved. So that SMEs and so on, can can thrive. So this is things like you know, the MHRA working as effectively as possible, you know, nice having clarity in terms of those kinds of technologies, which they want to pull in, but also an adoption pathway, which is much more effective and welcoming. And there's, there's different things that can be done to make that work. And I think we all know that there are challenges with, you know, our mocks and local prescribing committees, reconsidering the views of nice and so on. And so you have many layers of bureaucracy, which can be definitely improved. And I know that a lot of that is being looked at at the moment. The second area is, of course, making data accessible when this is, you know, an appropriate thing to do. And we have a long way to go in terms of that. And I know that there is a tre plan to do this, but it will take a while for that to come online. And so we need interim measures to make sure that we have site safe access and appropriate access to data and open safely was a great example of how that can be done. And we we I think what we want to have is from government and NHS Trusts and appropriate approach to feel as though they can take the risk and share the risk of letting letting data flow safely and ethically. So there's, there's a number of those elements which are in that. And so I feel positive about that. And I know we're going to talk about this a little bit later. But all of this is dependent on having very strong and cross party honestly support for the life sciences sector, so that all of these commitments get delivered on because there's a huge amount of funding, which is there for health data infrastructure to unlock all of the data infrastructure for Health Research, and the different levels of support for an AI hub and so on like that, and also making sure that, you know, our various different bits of genomic infrastructure, which will unlock the the underlying infrastructure for the SMEs to thrive above it, whether it's biobank or gel or our future health. And my very strong impression is, no matter how many health ministers or Secretaries of State or chancellors we have, the one thing you can rely on is the life sciences sector is understood to be the most productive and high growth sector within our economy. And it is one which has high levels of inward investment, and therefore, economic recovery is dependent on support for this. So my view is that the life sciences vision, the rare disease framework will survive and be highly prioritised. And so going with the grain of that, and understanding that, that's where you can find your opportunities is definitely encouraging. Because you won't see suddenly the rug pulled out and a complete change of policy and direction. And this matters, because NHS Trusts and the new ICVs. And all that structure, they will act according to these high level policy documents. And it's how the money flows down. And it's how the procurement flows out, if that makes sense.

Patrick Short  26:02  
Yes, yes, it absolutely does. So it sounds like even though it's been a turbulent, last couple of years politically, the life sciences strategy is really part of the core that because I think you make a really important point, which is that the UK is I think, very much still ahead of the game compared to most other countries in terms of integrating genomics into healthcare and life science as an as an economic force in the country. But we can't rest on that on that lead, right? It investment has to continue. And if we take our eye off the ball, so to speak, then that could very quickly change. But it sounds like what you're saying is, it has historically and likely will continue to be a really core part of the national conversation in the country. Is that right?

Baroness Nicola Blackwood  26:47  
I mean, the conversations that I've had with the current Secretary of State with, I mean, we know that the chancellor is supportive, because he's a former health secretary and was part of the start of the genomics programme. But also with the current secretary database. They are huge fans of genomics. They see this as the hope for turning around some of the challenges in the NHS, they want to move to prevention, which is about targeted and personalised medicine and understanding risk stratification, so they do get it now operationalizing that within the NHS and understanding how you deliver it, we have certain roadmaps, those roadmaps are the rare disease framework, and they are the life sciences vision. So if you are a young company within the UK, using those to understand that this is where the money flows, and this is how certain your buyers, essentially within the market will have their decisions, segmented is helpful.

Patrick Short  27:52  
Yeah, couldn't agree more. Maybe just to close out here, it'd be really great to hear your view on what are the couple of areas that you're most excited about. Over the next decade, I think prevention that you just named is a really clear and interesting one, we had Professor Peter Donnelly on the podcast relatively recently talking about some of the integration of genomics, PLCs, risk scores, and some some tests that are happening in the NHS. I know there's a big programme in early cancer detection with Grail that's happening, it'd be great to hear about the two or three areas that you think if rare disease diagnostics, maybe it's one I would nominate for the past decade, having come an extremely long way. And I think there's still a tonne of work to be done there. But as you mentioned before, we're we're now whole genome sequencing, the Genomic Medicine Service is up and running in the country, I'm so interested to hear what the next two or three waves are, if we were to do this podcast in a couple of years and look back on this time, what it would be,

Baroness Nicola Blackwood  28:46  
understandably, I am very, very excited about our newborn genome programme. I think this has enormous potential to catch not just those rare disease patients, but transform the way in which we deliver healthcare in the long term. So that I think is a health transformation programme, that will have enormous benefits in the long term, and will enable risk stratification not just for rare diseases, but for common diseases as well. So that one for me is one to watch. The second area in which I'm super interested, is around the use of sequencing for pathogens, which will allow the you know, the targeted use of antibiotics, because I think AMR is not going anywhere. And we've kind of forgotten about it. But I think until we can find really effective ways to address that. And I know that there's a trial going on in some ICUs in the country with with nanopore on that I think that's super exciting. And if we can start doing that we could really find our way out of this challenge. So that's one. And then the other area, of course, is our ability to end the diagnostic odyssey Just like for me, the ending of the diagnostic odyssey is like my North Star, if we could do that, and it really feels within reach right now, ending the diagnostic odyssey, and having a therapeutic out the end of it for patients. So genomics England is in a partnership with the Oxford Harrington Centre in Oxford, who have a pathway to developing therapeutics. So this isn't just about the diagnostic, it's about the clinical pathway. And for me, in a in a disease area where in a, in an area where you only have 5% of therapeutics, it's not it's not enough for a patient, just to get the diagnostic, you need to have a way to live afterwards. And so that's the exciting one for me is that we're starting to create a route out for all of these patients who have been, you know, stumbling around health systems with no answers. And I think we're, over the next decade, we may start to see a real a real shift in the way in which rare disease patient experience is healthcare.

Patrick Short  31:05  
Is there any final one because I can't resist there, the Orphan Drug Act and other associated legal frameworks have I think, been an enormous tailwind to rare disease, drug development, right, that has made it economically much more attractive for drug companies to focus on these diseases. But as you mentioned before, we're still only 5% of the way there. So there's a very long way to go. I'm wondering if you have thoughts on from a policy perspective and kind of orphan Orphan Drug Act 2.0. What could we do to do that more quickly? Because I think we do, frankly, still face the challenge right now that most rare diseases are too small to be attractive markets for many pharma and biotech companies. And maybe that's, you know, maybe that will change as the technology matures, but interested in whether you have ideas around how we can make those markets more attractive, because ultimately, we know that that patients need it, but it's just not happening at the pace that I think either of us would like.

Baroness Nicola Blackwood  32:06  
So I so this is these, this is the modelling that's going on at the moment about risk risk sharing models. And my understanding is that treasuries which have, until this point, really refused to engage on it are starting to look at it. And so I think about so watch this space, sort of question, because until now, there has not been the imperative with health systems that are kind of on a burning platform to really start thinking the unthinkable, and really reevaluating, from first principles, all the different models of which they are operating, when you have a health system in which one in nine people in the country are on a waiting list, and ambulance waiting times have tripled. And you can't get people out of the system, all of a sudden, all the ideas which would never have been considered before are on the table. And so we are in a different policy climate today. And that is why, you know, when when the climate becomes like this, it is obviously very stressful and difficult for patients. But it is also a moment when change can happen. Because policy makers are open for finding radical solutions, which perhaps can create the change which has been needed world.

Patrick Short  33:26  
Great. Well, thank you. I am going to watch all those three areas that you mentioned and I appreciate a you taking the time to do this but also for you dedicating such a big portion of your life and career to working on this important challenge. So it's really come a long way I think in the last decade and excited for more progress in the in the coming years.

Baroness Nicola Blackwood  33:46  
No problem. It's been it's been great to talk to you. Thank you so much for your time, Patrick.

Patrick Short  33:49  
Great, and thanks everyone for listening. If you enjoyed this episode, please feel free to share it out. Leave us a review and if you have any guests recommendations anyone you'd like to hear from actually Nicola came from a guest requests to somebody they really liked to hear from so please do get in touch. We're at podcasts at sound genetics.com Thanks again and we'll see you next time.

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